Thus far only one strategy to postpone age-related cognitive impairment has proven to be effective in a randomized controlled trial: the intensive SBP lowering intervention in SPRINT. While the Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated a positive effect of intensive blood pressure control for lowering rates of mild cognitive impairment (MCI), results were not conclusive for probable dementia. The estimated reduction in risk for probable dementia was in the same direction and of the same magnitude as for MCI (19% p=0.008) but the hazard ratio estimate for probable dementia was not statistically significant (17%, p=0.10). Uncertainty surrounding the effect on dementia, as opposed to MCI, could be addressed by conducting another trial, but changes in the BP guidelines make it doubtful that another large scale trial in US adults will examine the cognitive impact of treating SBP in older persons to <120 mm Hg versus <140 mm Hg. Therefore, additional follow-up of the SPRINT cohort provides a unique opportunity for testing hypotheses on how blood pressure control affects cognitive function. Some of the expected follow-up on cognitive function was curtailed when the trial intervention was stopped early, but SPRINT ASK funded an additional assessment that made the total length of follow-up consistent with the original SPRINT design. However, SPRINT ASK fell short of ascertaining the number of cases needed for a definitive test of the effect on probable dementia. This renewal proposal will obtain an additional follow-up assessment and address important questions related to lower SBP goals. We will attempt to assess every SPRINT participant who we have consent to contact starting in 2020. The assessments will be conducted via the telephone-based approach that was successful in ASK and by face-to-face visits. The telephone-based cognitive test battery, which has been previously validated and used in other cohort studies and clinical trials of cognition, will be supplemented with an in-person battery. A finding of benefit for probable dementia in addition to MCI would greatly strengthen the clinical message on the potential for treatment of hypertension to prevent cognitive decline. Alternatively, a finding of no impact on all-cause dementia, or a decreased effect on MCI would also provide important evidence to inform clinical decision-making. In either case, the SPRINT cohort is uniquely placed for a low cost opportunity to determine efficacy of therapy for BP lowering for improving cognitive health in our aging population.
SPRINT MIND 2020 Project Narrative Alzheimer's disease has been estimated to effect >46 million individuals globally and 5.8 million persons in the United States. This number is expected to double by 2050. Thus far only one strategy to prevent age-related cognitive impairment has proven to be effective in a randomized controlled trial: the intensive SBP lowering intervention in SPRINT. By obtaining an additional visit with the SPRINT cohort, the proposed study would provide important evidence to inform clinical decision-making on the potential for treatment of hypertension to postpone cognitive decline.
| Rizvi, Ali A (2017) ADDRESSING HYPERTENSION IN THE PATIENT WITH TYPE 2 DIABETES MELLITUS: PATHOGENESIS, GOALS, AND THERAPEUTIC APPROACH. Eur Med J Diabetes 5:84-92 |
| Valencia, Willy Marcos; Palacio, Ana; Tamariz, Leonardo et al. (2017) Metformin and ageing: improving ageing outcomes beyond glycaemic control. Diabetologia 60:1630-1638 |
